Sitafloxacin [the name based on International Nonproprietary Names (INN) will hereinafter be used] is a compound (Japanese Registered Patent No. 2714597) having the following chemical structure: This compound has remarkably high antibacterial activities and is highly safe, so this compound under development is expected to serve as excellent quinolone synthetic antibacterials. Sitafloxacin was registered as a 3/2 hydrate under the Japanese Accepted Name (JAN). This 3/2 hydrate can be used as a sitafloxacin raw material for preparing the solid preparation of the present invention. However, it is also possible to use other types of sitafloxacin raw material, such as an anhydride, acid addition salt and carboxylate thereof.
In recent years, there has been a growing demand for the improvement of oral solid preparations, aimed to make their use more convenient to patients by reducing the number of times of dosage. In fact, improved administration methods, by which patients can reduce the number of times of dosage to as low as once per day, are prevalent in recent years. In foreign countries, particularly like European countries and the United States of America, solid preparations are generally required to contain an active ingredient at a high concentration, because people in these countries are relatively larger in their physique (body weight). For that reason, it has become necessary to obtain the solid preparations having a high concentration of an active ingredient per unit dosage. However, it turned out to have several problems such that the absorption of an active ingredient from the digestive tract is insufficient and the concentration of an active ingredient in blood varies widely, while there are no such problems with other solid preparations in which an active ingredient is contained at a small concentration. For example, sitafloxacin is known to have such tendency. More specifically, it has become apparent that some of the patients treated with the conventional solid preparations containing sitafloxacin at a high concentration are susceptible to the foregoing problems associated with the oral absorption (absorption from the digestive tract).
As a means for improving the absorption from the digestive tract, it is possible to rely on the preparations having excellent ability to disintegrate per se. In the case of sitafloxacin, however, there is no specific problem in disintegration even when incorporated in a solid preparation, and it was also confirmed that the solid preparations with excellent disintegration could be readily obtained as desired. Thus it proved that poor disintegration of a solid preparation is not responsible for a malfunction in the absorption from the digestive tract.
As another means for enhancing the absorption from the digest tract, there are the classical methods that can improve the solubility by processing an active agent, for instance, the method of pulverizing an active ingredient, the method of utilizing a solid dispersion with a high-molecular compound and the method of preparing a clatherate compound with cyclodextrin.
For the antibiotics of β-lactam type, there is a method that is capable of improving the absorption from the digestive tract by use of citric acid or cyclodextrin.
However, when used with sitafloxacin, citric acid could have a problem concerning compatibility to sitafloxacin. On the other hand, when cyclodextrin is incorporated, the composition needs to contain a large amount of this compound, to form a clatherate. The use of cyclodextrin is therefore not practical.
An object of the present invention is therefore to provide a solid preparation which contains an active ingredient at a high concentration and is free from problems in absorption from the digestive tract, more specifically, problems such as lowering of availability of the active ingredient due to poor absorption and wide variation of blood level of the active ingredient.